The objective of this project is to better understand the role of nucleic acid modification in the induction of tumors by chemical carcinogens. Attention will be focused on arylhydroxamic acid acyltransferase-catalyzed introduction of arylamine groups into nucleic acids. Structural modifications resulting from the formation and breakdown of arylamine-substituted nucleic acids will be characterized and the biochemical consequences of these modifications determined. Phosphotriester formation, as well as base alteration, will be studied. Techniques that utilize synthetic reactive species, purified metabolic activation systems, intact cells and in vivo administration of carcinogens will be employed. Experiments in vitro and in vivo will examine the biosynthesis and disposition of these adducts to learn more of the qualitative and quantitative importance of acyltransfer and other metabolic pathways in tissues that differ in their susceptibility to aromatic amines. The relative carcinogenicities of arylhydroxamic acids that differ in their potential for activation by acyltransferase will be determined in order to evaluate the biological role of this metabolic pathway in aromatic amine carcinogenesis.